Very short-term effects of a single dose of a proprotein convertase subtilisin/kexin 9 inhibitor before percutaneous coronary intervention: A single-arm study

Article

Author: Ikeda, Hiroyuki ; Miyoshi, Machiko ; Shiomi, Yuichiro ; Yamaguchi, Junya ; Sato, Yusuke ; Uzui, Hiroyasu ; Kataoka, Tatsuhiro ; Hasegawa, Kanae ; Tama, Naoto ; Tada, Hiroshi ; Morishita, Tetsuji ; Ishida, Kentaro ; Shimizu, Tomohiro

BACKGROUND AND AIMSThe short-term (within 6 weeks) effects of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors on lipid plaques have not been adequately evaluated. We aimed to investigate whether a single dose of a PCSK9 inhibitor before percutaneous coronary intervention (PCI) could reduce the abundance of lipid-core plaques identified via near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) at target lesions within a very short period.METHODSThis prospective, single-arm, single-center interventional study enrolled 27 consecutive patients with coronary artery disease. These patients underwent NIRS-IVUS during coronary angiography and repeat NIRS-IVUS during PCI performed between 2 and 6 weeks after the single-dose administration of 420 mg evolocumab. Changes in lesion lipid-core burden index (LCBI) and maximal LCBI over any 4-mm segment (max-LCBI_4mm) were assessed using NIRS at the target lesions, along with lipid profile.RESULTSThe max-LCBI_4mm significantly decreased from 387 before PCSK9 inhibitor administration to 315 after its administration (interquartile range [IQR]: 268-572 and 221-488, respectively; p = 0.02) within a very short period. The lesion LCBI also decreased from 161 to 117 (IQR: 105-263 and 65-226, respectively; p = 0.02). No significant changes were observed in the minimum lumen area and diameter. After PCSK9 inhibitor administration, low-density lipoprotein (LDL) cholesterol (p < 0.001), lipoprotein(a) (p = 0.001), and malondialdehyde-modified LDL (p < 0.001) levels decreased compared with those before its administration.CONCLUSIONSA single dose of the PCSK9 inhibitor administered before PCI reduced the abundance of lipid-core plaques identified via NIRS-IVUS at target lesions within a very short period of 2-6 weeks.

01 Jan 2024·Clinical nephrology. Case studies

A rare case of alirocumab (PCSK9 inhibitor)-associated acute interstitial nephritis.

Article

Author: Mehta, Swati ; Lightle, Andrea ; Habib, Nazia ; Yuan, Chase ; Monrroy, Mauricio

Acute interstitial nephritis (AIN) is a common cause of hospital-acquired acute kidney injury (AKI) [1]. The most common cause of AIN is drug-induced AIN, which accounts for 60 - 70% of cases [2]. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9 inhibitor) is a monoclonal antibody that lowers low-density lipoprotein-C levels by inhibiting the PCSK9 protein [3]. Common adverse events reported with alirocumab include injection-site reactions, myalgia, neurocognitive disorders, and ophthalmologic disorders [4]. There is paucity of data, with few reported cases of AKI, mostly in the form of acute tubular necrosis (ATN) associated with alirocumab [5]. In this article, we present a novel case of AIN associated with the use of alirocumab.

03 Oct 2022·Expert Review of Clinical Pharmacology

The role of PCSK9 in NAFLD/NASH and therapeutic implications of PCSK9 inhibition

Review

Author: Sahebkar, Amirhossein ; Momtazi-Borojeni, Amir Abbas ; Banach, Maciej ; Ruscica, Massimiliano

INTRODUCTIONThere are inconsistent findings regarding the effect of lipid-lowering agents on nonalcoholic fatty liver disease (NAFLD). Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) is an important player in cholesterol homeostasis and intracellular lipogenesis, and PCSK9 inhibitors (PCSK9-i) have been found to be efficient for pharmacological management of hyperlipidemia.AREAS COVEREDWhether PCSK9 (itself) or PCSK9-i affects NAFLD is still disputed. To address this question, we review published preclinical and clinical studies providing evidence for the role of PCSK9 in and the effect of PCSK9-I on the development and pathogenesis of NAFLD.EXPERT OPINIONThe current evidence from a landscape of preclinical and clinical studies examining the role of PCSK9 in NAFLD shows controversial results. Preclinical studies indicate that PCSK9 associates with NAFLD and nonalcoholic steatohepatitis (NASH) progression in opposite directions. In humans, it has been concluded that the severity of hepatic steatosis affects the correlation between circulating PCSK9 and liver fat content in humans, with a possible impact of circulating PCSK9 in the early stages of NAFLD, but not in the late stages. However, data from clinical trials with PCSK9-i reassure to the safety of these agents, although real-life long-term evidence is needed.

100 Deals associated with PCSK9 inhibitor(Nyrada Inc)

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Indication	Highest Phase	Country/Location	Organization	Date
Hypercholesterolemia	Preclinical	AU	Nyrada, Inc.	01 Nov 2022

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